Many proteins exert an effect on cell growth, differentiation, and inflammation through signal transduction, mediated by binding to a cell surface receptor. Yet other proteins, such as factors that initiate or are necessary for blood clot formation, act enzymatically in blood. While these actions are generally part of normal processes, under certain circumstances, it may be desirable to limit or inhibit the action of certain proteins and the effects of subsequent signaling. For example, tumor growth that is promoted by a growth factor, such as FGF-2 (fibroblast growth factor 2 or basic fibroblast growth factor) acting on melanoma cells, is deleterious and often leads to fatalities. Moreover, in tumorigenesis mediated by FGF-2, its transport to the nucleus is likely a requisite.
FGF-2 is expressed as four different isoforms, three of which are transported to the nucleus, while the fourth is exported by a non-classical pathway of secretion. The discovery that different isoforms of fibroblast growth factor 2 (FGF-2) localize to different cellular compartments offers the opportunity to develop therapeutics that alter trafficking patterns. For example, decreasing the amount of FGF-2 that moves into the nucleus may slow or halt growth of tumor cells. Thus, identification of specific inhibitors for nuclear trafficking of FGF-2, or other proteins, may prove useful in therapeutic applications.
The present invention discloses components of nuclear trafficking and inhibitors of nuclear transport, especially the nuclear transport of FGF-2, allowing control of undesired proliferation and inflammation, as well as other related advantages.